Peyssonnosides A–B, Unusual Diterpene Glycosides with a Sterically Encumbered Cyclopropane Motif: Structure Elucidation Using an Integrated Spectroscopic and Computational Workflow

Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonneliasp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A–B (1–2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.01,10.05,9] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium bergheiand moderate antimethicillin-resistant Staphylococcus aureus(MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1showed strong growth inhibition of the marine fungus Dendryphiella salinaindicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.